p62蛋白的分子功能及其在疾病中的研究进展

Advances in molecular function of p62 protein and its role in diseases

摘要:

螯合体1 (SQSTM1/p62)是一种选择性自噬接头蛋白，在清除待降解蛋白、维持细胞内蛋白质稳态中发挥重要的调控作用。p62蛋白具有多个功能结构域，介导与多种蛋白质发生相互作用进而精确调节特定的信号通路，从而将p62蛋白与氧化防御系统、炎症反应和营养感知等重要生命过程联系起来。研究表明p62的突变或者表达异常与多种疾病的发生发展过程密切相关，包括神经退行性疾病、肿瘤、感染性疾病、遗传性疾病以及慢性疾病等。本文综述了p62蛋白的结构特征、分子功能，并系统介绍其在蛋白质稳态和信号通路调控中的多种功能，总结了p62在疾病发生发展中的复杂性与多面性，以期为p62蛋白的功能与相关疾病研究提供参考。

关键词:SQSTM1/p62;蛋白酶体;自噬;疾病;肿瘤

Abstract:

Sequestosome 1 (SQSTM1/p62) is a selective autophagy adaptor protein that plays an important role in the clearance of proteins to be degraded as well as in the maintenance of cellular proteostasis. p62 protein has multiple functional domains, which interact with several downstream proteins to precisely regulate multiple signaling pathways, thereby linking p62 to oxidative defense systems, inflammatory responses and nutrient sensing. Studies have shown that mutation or abnormal expression of p62 is closely related to the occurrence and development of various diseases, including neurodegenerative diseases, tumors, infectious diseases, genetic diseases and chronic diseases. This review summarizes the structural features and molecular functions of p62. Moreover, we systematically introduce its multiple functions in protein homeostasis and regulation of signaling pathways. Furthermore, the complexity and versatility of p62 in the occurrence and development of diseases are summarized, with the aim to provide a reference for understanding the function of p62 protein and facilitating related disease research.

Key words:SQSTM1/p62;proteasome;autophagy;disease;tumor